Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project.

BACKGROUND: Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking. OBJECTIVE: To assess the association between the Testosterone (T)-to-Estradiol (E2) Ratio (T/E2) and platelet activation biomarkers in IHD and its predictive value on adverse outcomes. METHODS: The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary angiography and/or percutaneous coronary interventions. Serum T/E2 ratios E2, levels of thromboxane B2 (TxB2) and nitrates (NO), were measured at admission and major adverse events, including all-cause mortality, were collected during a long-term follow-up. RESULTS: Among 509 adults with IHD (mean age 67 ± 11 years, 30% females), males were older with a more adverse cluster of cardiovascular risk factors than females. Acute coronary syndrome and non-obstructive coronary artery disease were more prevalent in females versus males. The lower sex-specific T/E2 ratios identified adults with the highest level of serum TxB2 and the lowest NO levels. During a median follow-up of 23.7 months, the lower sex-specific T/E2 was associated with higher all-cause mortality (HR 3.49; 95% CI 1.24-9.80; p = 0.018). In in vitro, platelets incubated with T/E2 ratios comparable to those measured in vivo in the lowest quartile showed increased platelet activation as indicated by higher levels of aggregation and TxB2 production. CONCLUSION: Among adults with IHD, higher T/E2 ratio was associated with a lower long-term risk of fatal events. The effect of sex hormones on the platelet thromboxane release may partially explain such finding.

Aging and Adherence to the Mediterranean Diet: Relationship with Cardiometabolic Disorders and Polypharmacy.

OBJECTIVES: To investigate the association between adherence to the Mediterranean Diet (Med-Diet), cardiometabolic disorders and polypharmacy. DESIGN: Cross-sectional study. SETTING: Geriatrics outpatient clinic, Policlinico Umberto I, Sapienza University of Rome. PARTICIPANTS: 508 patients (219 male, 289 female) aged 50 to 89 who were evaluated for cardiovascular and metabolic disorders. METHODS AND MEASUREMENTS: Patients underwent a comprehensive medical assessment including medical history and the use of medications. Adherence to Med-Diet was assessed using the validated Med-Diet 14-item questionnaire; for the analysis, patients were divided in high (≥8) and medium-low (<8) adherence. Polypharmacy was defined as taking ≥5 medications. RESULTS: 476 patients completed the study. Mean age was 70.4 years; 58% female. Median Med-Diet score was 8 (interquartile range, 6-9). Patients with medium-low adherence had higher body mass index (p=0.029) and higher prevalence of arterial hypertension (p<0.001), previous coronary (p=0.002) and cerebrovascular events (p=0.011), diabetes, (p<0.001) and dyslipidemia (p=0.001) compared to those at high adherence. Med-Diet score decreased with the number of cardiometabolic disorders (p<0.001). The prevalence of polypharmacy was 39%. Consumption of olive oil (p=0.005), vegetables, (p<0.001), wine (p=0.017), legumes (p=0.028), fish (p=0.046) and nuts (p=0.045) were all inversely associated with the overall number of medications. In a multivariable regression model, medium-low adherence to Med-Diet was independently associated to polypharmacy (O.R.:1.859; 95% CI 1.142 to 3.025; p=0.013), after adjusting for possible confounding factors. CONCLUSION: Med-Diet was inversely associated with cardiometabolic disorders and with polypharmacy, suggesting that improved Med-Diet adherence might potentially delay the onset of age-related health deterioration and reduce the need of multiple medications.

Adenovirus 36 DNA in human adipose tissue.

Recent studies have suggested a possible correlation between obesity and adenovirus 36 (Adv36) infection in humans. As information on adenoviral DNA presence in human adipose tissue are limited, we evaluated the presence of Adv36 DNA in adipose tissue of 21 adult overweight or obese patients. Total DNA was extracted from adipose tissue biopsies. Virus detection was performed using PCR protocols with primers against specific Adv36 fiber protein and the viral oncogenic E4orf1 protein nucleotide sequences. Sequences were aligned with the NCBI database and phylogenetic analyses were carried out with MEGA6 software. Adv36 DNA was found in four samples (19%). This study indicates that some individuals carry Adv36 in the visceral adipose tissue. Further studies are needed to determine the specific effect of Adv36 infection on adipocytes, the prevalence of Adv36 infection and its relationship with obesity in the perspective of developing a vaccine that could potentially prevent or mitigate infection.

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects.

OBJECTIVES: Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive. DESIGN: We tested the effect of EVOO, added to Mediterranean-type meal, on post-prandial glycemic and lipid profile. SUBJECTS: Post-prandial glycemic and lipid profile were investigated in 25 healthy subjects who were randomly allocated in a cross-over design to a Mediterranean-type meal added with or without 10 g EVOO (first study), or Mediterranean-type meal with EVOO (10 g) or corn oil (10 g; second study). Glycemic profile, which included glucose, insulin, dipeptidyl-peptidase-4 (DPP-4) protein and activity, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and lipid profile, which included, low-density lipoprotein (LDL) cholesterol (LDL-C), oxidized LDL (ox-LDL), triglycerides and high-density lipoprotein (HDL) cholesterol (HDL-C), were analyzed before and 2 h after the meal. RESULTS: In the first study, 2 h after meal, subjects who assumed a meal with EVOO had significantly lower blood glucose (P<0.001), DPP-4 protein (P<0.001) and activity (P<0.001), LDL-C (P<0.001) and ox-LDL (P<0.001) and higher insulin (P<0.05), GLP-1 (P<0.001) and GIP (P<0.05) compared with those without EVOO. The second study showed that compared with corn oil, EVOO improved both glycemic and lipid profile. Thus, a significantly smaller increase of glucose (P<0.05), DPP4 protein (P<0.001) and activity (P<0.05) and higher increase of insulin (P<0.001) and GLP-1 (P<0.001) were observed. Furthermore, compared with corn oil, EVOO showed a significantly less increase of LDL-C (P<0.05) and ox-LDL (P<0.001). CONCLUSIONS: We report for the first time that EVOO improves post-prandial glucose and LDL-C, an effect that may account for the antiatherosclerotic effect of the Mediterranean diet.

Pneumonia, thrombosis and vascular disease.

SUMMARY: An enhanced risk of cardiovascular mortality has been observed after pneumonia. Epidemiological studies have shown that respiratory tract infections are associated with an increased risk of thrombotic-related vascular disease such as myocardial infarction, ischemic stroke and venous thrombosis. Myocardial infarction and stroke have been detected essentially in the early phase of the disease (i.e. within 48 h from hospital admission), with an incidence ranging from as low as 1% to as high as 11%. Age, previous cardiovascular events and high pneumonia severity index were independent predictors of myocardial infarction; clinical predictors of stroke were not identified. Deep venous thrombosis and pulmonary embolism may also occur after pneumonia but incidence and clinical predictors must be defined. The biological plausibility of such an association may be deduced by experimental and clinical studies, showing that lung infection is complicated by platelet aggregation and clotting system activation, as documented by up-regulation of tissue factor and down-regulation of activated protein C. The effect of antithrombotic drugs has been examined in experimental and clinical studies but results are still inconclusive.

Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer.

Deregulated expression of ETS transcription factors has emerged as an important event in prostate cancer pathogenesis. Here we show that the expression of epithelial-specific ETS (ESE)-3 factor is frequently reduced at the RNA and protein level in prostate cancer clinical samples compared to normal prostate. In PC3 and DU145 cells, ESE-3 was silenced by methylation of an evolutionarily conserved CpG site in its promoter and treatment with 5-aza-2'-deoxycytidine restored its expression. In a prostate epithelial cell transformation model, methylation of this site was inversely correlated with ESE-3 expression and occurred only in Ras-transformed and tumorigenic cells and not in normal and immortalized cells suggesting that ESE-3 silencing was functionally linked to oncogenic transformation. Consistent with a tumor suppressor function, re-expression of ESE-3 in prostate cancer cells inhibited clonogenic survival and induced apoptotic cell death. ESE-3 increased the level of procaspase-3, a key element in the apoptotic cascade. This effect was mediated at the transcriptional level by direct binding of ESE-3 to the caspase-3 promoter. Collectively, our findings implicate ESE-3 as a candidate tumor suppressor in prostate cancer. Decreased expression of ESE-3 may result in loss of important regulatory mechanisms in prostate epithelial cells and contribute to the pathogenesis of prostate cancer.

Risk of mortality from cardiovascular and respiratory causes in patients with chronic obstructive pulmonary disease submitted to follow-up after lung resection for non-small cell lung cancer.

AIM: Considerable controversy surrounds mortality from non-neoplastic diseases during the postoperative follow-up of patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). This study investigated the incidence of mortality from cardiovascular and respiratory (CVR) causes in patients with COPD submitted to follow-up after lung resection for NSCLC, and identified preoperative and postoperative risk factors. METHODS: A total of 398 patients with mild or moderate COPD were followed up in our department after lung resection for NSCLC (median follow-up 61 months). Statistical analysis of the data was carried out to determine the incidence and the prognostic factors of postoperative death from CVR causes. RESULTS: Of the 398 resected patients, 186 survived without tumor recurrence; 24/186 (12.9%) died of CVR causes (acute respiratory failure, pneumonia, pulmonary embolism, acute pulmonary edema, acute myocardial ischemia or stroke). These 24 patients had a higher frequency of pre-existing coronary artery disease or heart failure (P=0.0003), predicted postoperative FEV1 <1000 mL (P=0.0008), exertional dyspnea (P=0.0000), and 30-day operative cardiopulmonary complications (P=0.001). Protective features were young age (<40 years), early stage disease, and minor resection (lobectomy). Independently significant adverse prognostic factors were stage III-IV disease (cumulative CVR death rate 47% at 5-10 years; P=0.028 vs. stage I-II) and completion pneumonectomy or partial resection of the other lung for a second primary tumor (cumulative CVR death rate 50% and 57%, respectively, at 5-10 years; P=0.0016 vs. all other resections). Older age and tumor histology were significant risk factors only in patients with advanced stage disease. CONCLUSION: The findings suggest that postoperative CVR death may be expected in patients with COPD and advanced stage NSCLC or in those undergoing completion pneumonectomy or partial resection of the other lung for a second primary tumor. Other risk factors are previous coronary artery disease and/or heart failure, exertional dyspnea and predicted postoperative FEV1 <1000 mL.

Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease.

AIMS: To investigate the existence of a relationship among flow-mediated dilation (FMD), nitric oxide (NO), and oxidative stress in patients with peripheral arterial disease (PAD), and to assess if the administration of an antioxidant was able to improve arterial dilatation. METHODS AND RESULTS: We performed a cross-sectional study comparing FMD, 8-Hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress, and nitrite/nitrate (NOx) serum levels in a population of 25 PAD patients and 40 controls. In the second part of the study, 21 PAD patients were randomly allocated to a treatment sequence of 7 days of i.v. infusion of placebo or 6 g/day propionyl-L-carnitine (PLC) in a cross-over design. Compared with controls, patients with PAD had enhanced 8-OHdG serum levels (2.4 +/- 1.2 vs. 4.24 +/- 3.11 ng/mL; P < 0.001), reduced NOx (17.02 +/- 6.11 vs. 11.28 +/- 6.02 microM; P < 0.001), and lowered FMD (10.34 +/- 2.14 vs. 6.69 +/- 2.95; P < 0.001). PLC infusion was associated with an increase of FMD [from 6.6 +/- 0.6 to 11.1 +/- 1.2% (mean +/- SE), P = 0.004] and NOx (from 14.5 +/- 1.4 to 17.1 +/- 1.2 microM; +18%, P = 0.012) and a decrease of 8-OHdG (from 3.62 +/- 0.37 to 2.64 +/- 0.32 ng/mL; -27%, P < 0.001). No changes were observed after placebo treatment. CONCLUSION: This study shows that in PAD patients, oxidative stress is implicated in determining reduced FMD.

Enhanced soluble CD40L in patients with the metabolic syndrome: Relationship with in vivo thrombin generation.

AIMS/HYPOTHESIS: The metabolic syndrome is associated with proinflammatory and prothrombotic states. This study was designed to assess the behaviour of soluble CD40 ligand (sCD40L) and prothrombin fragment F (1+2), a marker of thrombin generation, in patients with the metabolic syndrome. METHODS: We investigated 106 patients with the metabolic syndrome, diagnosed according to the ATPIII report, and 104 subjects without the metabolic syndrome. RESULTS: Plasma values of sCD40L and F (1+2) were higher in patients with the metabolic syndrome (4.11+/-1.64 vs 2.61+/-0.89 ng/ml and 1.54+/-0.49 vs 0.87+/-0.21 nmol/l, respectively; p < 0.001) and were significantly correlated (r = 0.925, p < 0.001). Stepwise multiple linear regression analysis showed that sCD40L was significantly associated with F (1+2), female sex and waist circumference. CONCLUSIONS/INTERPRETATION: Patients with the metabolic syndrome have enhanced values of plasma sCD40L and F (1+2). The study provides further insight into the relationship between metabolic syndrome, inflammation and thrombosis.

Specificity of antinuclear and antiphospholipid antibodies in sera of patients with autoimmune lymphoproliferative disease (ALD).

OBJECTIVE: A human lymphoproliferative syndrome characterized by a defect of the Fas-mediated apoptosis pathway in the absence of a fas gene mutation (Autoimmune Lymphoproliferative Disease) has recently been described and characterized by autoimmune phenomena. The aim of this study was to investigate the presence of antinuclear and antiphospholipid antibodies and to define their specificity in 5 pediatric patients with this syndrome. METHODS: Antinuclear antibodies were investigated by Western Blot and IIF performed under standard as well as apoptotic conditions. The fine specificity of antiphospholipid antibodies was dissected by an ELISA for anti-beta 2-glycoprotein I, anti-prothrombin, anti-annexin V and anti-protein S antibodies, and by immunostaining on thin layer chromatography plates for antiphospholipid molecule antibodies. RESULTS: This study showed that the autoantibodies found in these patients targeted a broad spectrum of nuclear antigens which undergo redistribution from the nucleus to the cytoplasm and plasma membrane during the course of the apoptotic process. This reactivity does not comprise known specificities such as anti-extractable nuclear antigens or anti-dsDNA. Antiphospholipid antibodies were also found in these sera. A further characterization of the antiphospholipid antibodies showed the presence of a heterogeneous response with antibodies directed to negatively-charged phospholipids and antibodies targeting coagulation-related proteins (beta 2-GPI, prothrombin, annexin V) which are considered relevant antigens in the antiphospholipid syndrome. CONCLUSIONS: These results suggest that lack of tolerance due to a defect of Fas-mediated apoptosis allows the survival of B and T clones involved in the antinuclear and antiphospholipid immune responses.

Giant diverticulum of the sigmoid colon with perforation. Report of a case.

We present a case of perforated giant diverticulum of the sigmoid colon. This condition is extremely rare and only a few cases have so far been reported in the literature. Our case involved a 55-year old woman. Diagnosis was easy with barium enema and CT scan examination. Laparotomy revealed a giant diverticulum of the sigmoid colon compressing adjacent structures with signs of inflammation. An en bloc resection of the sigmoid colon, ovary and fallopian tube was performed with primary colon-rectal anastomosis. The post-operative course was uneventful.

Ultrastructural studies on the respiratory tract of mice inoculated intranasally with L. fermentum.

The ultrastructural modifications of the respiratory tract of mice produced by the intranasally inoculated L. fermentum was evaluated. The genus Lactobacillus has been largely studied from the probiotic effect point of view in different ecological systems. Lactobacilli inoculated in 4 intranasal doses (1 x 10(9) CFU/dose) do not produce fundamental changes at the ultrastructural level in the organs of the respiratory tract studied. The most important finding was the presence of a cellular type with intracellular structures surrounded by membranes exhibiting electron dense paracristalline material parallel arranged.

Bronchioloalveolar carcinoma: clinical, radiographic, and pathological findings. Surgical results.

BACKGROUND: Bronchioloalveolar carcinoma (BAC) remains one of the most controversial of lung cancer subtypes. METHODS: From 1980 to 1998, 374 resected patients for NSCLC were followed up in our department. Of the 147 cases histologically defined as adenocarcinoma, 34 were pure BAC. The records of these 34 patients were retrospectively reviewed in order to evaluate patient and tumor characteristics and to identify which variables had a prognostic impact on survival and recurrence rate. RESULTS: Patient age, sex, smoking habits and symptoms were not differentiating characteristics when related to radiographic presentation or to natural history. Mucinous cell-type (23.6% of cases) was more frequent with non-smokers, presence of a single nodule or mass and stage I. Favorable characteristics were: a) the prevalence of stage I and N0 cases (59% and 76.7% of cases, respectively) with a mean survival time of 66 and 77 months, respectively; and b) the radiographic presentation of a solitary pulmonary nodule or mass (76.4% of cases), that, independently of nodal involvement, showed a higher mean survival time (62 months). Independently significant adverse prognostic factors were: stage II-IV, lymph node involvement, and patient age over sixty years. The radiographic presence of multiple or satellite nodules was related to a significantly adverse prognosis (mean survival time: 18 months) by univariate analysis; this was not confirmed by multivariate analysis. CONCLUSIONS: In our experience BAC was the NSCLC subtype more frequently associated with a good outcome after resection; surgery should not to be denied also in patients with multiple nodules, when under sixty years of age and no lymph node involvement.

Ultrastructural studies on the respiratory tract of mice inoculated intranasally with L. fermentum.

The ultrastructural modifications of the respiratory tract of mice produced by the intranasally inoculated L. fermentum was evaluated. The genus Lactobacillus has been largely studied from the probiotic effect point of view in different ecological systems. Lactobacilli inoculated in 4 intranasal doses (1 x 10(9) CFU/dose) do not produce fundamental changes at the ultrastructural level in the organs of the respiratory tract studied. The most important finding was the presence of a cellular type with intracellular structures surrounded by membranes exhibiting electron dense paracristalline material parallel arranged.

Technetium-99m tetrofosmin single photon emission computed tomography in the evaluation of suspected lung cancer.

Technetium-99m-tetrofosmin is a radiopharmaceutical employed for myocardial imaging, which has recently emerged as useful in the visualization of tumors. In this study technetium-99m-tetrofosmin was evaluated for its accuracy in differentiating malignant from benign pulmonary lesions, and in detecting mediastinal node metastasis due to lung cancer. Eighty-one patients with a solitary lung lesion on the chest radiograph and/or CT scan were submitted to chest single photon emission computed tomography after technetium-99m-tetrofosmin injection (740 MBq i.v.). The scintigraphic findings were correlated to the final histopathological diagnosis, demonstrating abnormal tracer accumulation in 51 of 54 malignant lesions (sensitivity 94%) and in 4 out of 27 benign conditions (specificity 85%), yielding an accuracy of 91%. Mediastinal lymph-node involvement was evaluated in 35 patients with non small cell lung cancer who underwent mediastinoscopy and/or surgery. Tetrofosmin accuracy (89%) was significantly higher than that of CT (69%, p < 0.05); the false negative scintigraphic results were in nodes sized less than 1 cm. In conclusion, technetium-99m-tetrofosmin imaging is useful in distinguishing malignant from benign pulmonary lesions, and in non-invasively assessing mediastinal node metastases from non small cell lung cancer, especially in patients with enlarged nodes by CT scan.

Carcinoma of the duodenum: management and survival in 14 cases.

AIMS: The aim of this study is to evaluate the role of surgery in the treatment of adenocarcinoma of the duodenum. METHODS: From 1955 to 1994, 14 patients with primary adenocarcinoma of the duodenum underwent surgical treatment in our department. Presenting signs and symptoms were mainly related to obstruction and bleeding. Upper gastrointestinal contrast study, Computed Tomography (CT) and duodenoscopy were the primary diagnostic procedure modalities. All diagnoses were confirmed histologically. The tumors were staged pathologically according to the new TNM classification (UICC, 1992). Eight patients received palliative treatment or exploratory laparotomy. The remaining 6 patients were resectable for cure. RESULT: Operative mortality was 35.7%. The 5-year survival rate for patients who underwent curative resection was 33.3%. None of the patients who underwent palliative procedures or exploratory laparotomy survived for more than 11 months. CONCLUSIONS: In the management of resectable adenocarcinomas of the duodenum surgical radicality including lymphadenectomy should be pursued. Unresectable adenocarcinomas treated with palliative procedure had a very poor prognosis.

Rhodococcus equi pneumonia in a patient with occult HIV infection: successful therapy.

We report a case of Rhodococcus equi cavitary pneumonia in a 37-year-old patient with occult HIV infection. Because of his good immune status, the patient was given oral erythromycin and rifampin which rapidly resolved the infection. This modality of treatment may be sufficient in HIV-positive selected patients fur the resolution of Rhodococcus equi pneumonia.

[The role of surgery in the treatment of primary carcinoma of the gallbladder. Review of 86 cases]. / II ruolo della chirurgia nel trattamento del carcinoma primitivo della colecisti. Revisione di 86 casi.

The records of 86 patients with primary adenocarcinoma of the gallbladder were reviewed. All patients were staged according to the Nevin classification. Twenty-nine patients underwent resection, 57 were submitted to palliative procedures or exploratory laparotomy. Survival was directly related to tumor staging and modality of treatment. The 5- and 10-year survival expectancy after curative resection was 46.8% in stage II patients, 14.2% and 0%, respectively, in stage V patients. None of the unresectable cases survived beyond 24 months, except for one patients who lived 62 months. No significant difference in survival expectancy was found between resectable and unresectable patients with stage V tumor.